Insulin-like growth factors-1 (IGF-1) and -2 (IGF-2) have been implicated in the pathophysiology of a wide range of human neoplasias due to the mitogenic and anti-apoptotic properties mediated by their type I receptor (IGF-1R or CD221). Expression of functional IGF-1R is required for neoplastic transformation in diverse tumorigenesis models. However, the art has not applied the inhibition of the IGF-1R pathway as a major anti-cancer therapeutic strategy, due, in part, to the lack of clinically-applicable small molecule inhibitors of IGF-1R function, and in part to the uncertainty of the clinical impact of inhibiting the IGF/IGF-1R pathway in tumor cell proliferation and survival. Moreover, widespread expression of IGF-1R in normal tissues raises concerns regarding the specificity and the toxicity of IGF/IGF-1R pathway inhibition.